The objective of this project is to evaluate the drug and hormonal sensitivity of the pre-capillary arterioles compared to post-capillary venuoles supplying individual chorionic villi of the full-term human placenta. Initially, this in vitro study will be performed under conditions reflecting the oxygen status believed to occur in-utero (PO2 25 torr). In addition, the ability of oxygen to modulate the resting and drug induced active tension developed by these micro-vessels will also be determined. Homologous vessels from pre-term placentas will be studied for their drug sensitivity and compared to full-term control vessels in order to assess the ontogenetic evolution of drug sensitivity from 0.5 gestation to term. The third phase of this study will examine the pre- and post-capillary placental vasculature from normal compared to certain high risk pregnancies with respect to drug sensitivity as well as histological evidence for vascular wall lipid accumulation and arteriolosclerosis. The purpose of this phase is to determine if this fetal vasculature, critical to normal fetal development, is involved in the pathophysiology of "enclamptic" disorders, gestational hypertension and/or intrauterine growth retardation. The final phase of this study will examine pre- and post-capillary fetal placental vasculature of various laboratory animals commonly used as experimental models of pregnancy. These findings will be compared with the findings in the human placenta in order to compare the phylogenetic aspects of placental vascular pharmacology between these animal models and man. This research will be performed by isolating helically cut strips of human placental villous stem arterioles and venuoles isometrically in Kreb's solution at 37 degrees C. The pO2 of the Kreb's solution will either be held between 20-25 torr, or varied between 1 and 100 torr, depending on the protocol, while holding pH and PCO2 constant. Dose-response curves will be constructed for each agonist and the peak tension developed and half maximum responses will be analyzed on a statistical basis. Information gained from this work will be integrated into the current knowledge of factors affecting the fetal umbilico-placental vasculature in an ongoing attempt by this investigator to construct a working hypothesis of the control of the placental vasculature in humans